Cardiovascular disease (CVD) is the number one cause of death globally. More people die annually from CVD than from any other cause. Smoking, hypertension, high LDL cholesterol, low HDL cholesterol and diabetes mellitus (DM) are the five major risk factors for CVD. Diabetes is associated with an increased risk of atherosclerosis, which may result in coronary artery disease (CAD) (A. Pandolfi, et al., “Chronic hyperglycemia and nitric oxide bioavailability play a pivotal role in proatherogenic vascular modifications,” Genes & Nutrition (2007) 2 (2): 195-208). Physiological impairments that link DM with a marked increase in atherosclerotic vascular disease include platelet hyper-reactivity, a tendency for negative arterial remodeling, impaired fibrinolysis, increased inflammation, and endothelial dysfunction.
Endothelial dysfunction, present at disease onset, may be the cause of atherogenesis that is present throughout the course of DM and associated with late-stage adverse outcomes (Panwar, et al., “Atherothrombotic risk factors & premature coronary heart disease in India: A case-control study,” Indian J. Med. Res. (July 2011) 134: 26-32). The endothelial dysfunction results from reduced bioavailability of the vasodilator nitric oxide (NO) mainly due to accelerated NO degradation by reactive oxygen species (J. A. Beckman, “Pathophysiology of Vascular Dysfunction in Diabetes,” Cardiology Rounds (December 2004) Volume 8, Issue 10). A currently favored hypothesis is that oxidative stress, through a single unifying mechanism of superoxide production, is the common pathogenic factor leading to insulin resistance, β-cell dysfunction, impaired glucose tolerance (IGT) and ultimately to Type 2 DM (T2DM). Furthermore, this mechanism has been implicated as the underlying cause of both the macrovascular and microvascular complications associated with Type 2 DM. It follows that therapies aimed at reducing oxidative stress would benefit both patients with T2DM and those at risk for developing diabetes (Potneza, et al., “Endothelial Dysfunction in Diabetes: From Mechanism to Therapeutic Targets,” Current Medicinal Chemistry (2009) 16: 94-112; S. E. Inzucchi, “Oral Antihyperglycemic Therapy for Type 2 Diabetes. Scientific Review and Clinical Applications,” Journal of American Medical Association (Jan. 16, 2002—Vol 287, No. 3, pp. 360-372; and Wright, et al., “Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia,” Int. J. Clin. Pract. (2006 March) 60(3): 308-314).
Many herbs possess potent antioxidant, anti-inflammatory and cardio-protective properties and are used by patients with increased risk of cardiovascular morbidity and mortality in order to treat or prevent disease and/or reduce symptoms. Among them, Phyllanthus emblica, syn. Emblica officinalis Gaertn., the Indian gooseberry (PE, “Amla”) is widely used in Indian medicine for the treatment of various diseases. There are studies which show significant anti-hyperglycaemic and lipid lowering effects of PE in diabetic patients. In in-vitro and animal studies, PE demonstrates potent antioxidant effects against several test systems such as superoxide radical and hydroxyl radical scavenging action, and in systemic augmentation of antioxidant enzymes in animals (Antony, et al., “A pilot clinical study evaluate the effect of Emblica officinalis extract (Amlamax™) on markers of systemic inflammation and dyslipidemia,” Indian J. Clin. Biochemistry (2008) 23(4): 378-381).
Withania somnifera (WS, Ashwagandha) is also widely used in Ayurvedic medicine for the treatment of various diseases. WS is an adaptogen and a rejuvenative that helps maintain proper nourishment of the tissues, particularly muscle and bone, while supporting the proper function of the adrenals and reproductive system. Although its therapeutic potential for immunumodulatory, adaptogenic, antioxidant, hypoglycemic and anticancer activities have been reported, very few studies assessing its cardio-protective potential are presently available (Malhotra, et al., “Studies on Withania somnifera (Part III). The effect of total alkaloid (Ashwagandholine) on CVS and respiration,” Ind. J. Med. Res. (1961) 49: 449; Lavie, et al., “Constituents of Withania somnifera Dun IV,” J. Chem. Soc. (1965) 12: 7517; and Dhuley, et al., “Adaptogenic and cardioprotective action of ashwagandha on rats and frogs,” J. Ethnopharmacol. (2000) 70: 57-63). There are clinical studies which have demonstrated the efficacy of WS in the treatment of hypercholesterolemia.
In view of the above, it would be desirable to provide a potent and therapeutically effective Phyllanthus emblica and/or Withania somnifera composition for use as a nutritional supplement.
If a way could be found to use a therapeutically effective amount of Phyllanthus emblica and/or Withania somnifera in a composition to treat or prevent endothelial dysfunction and/or diabetes, this would represent a useful contribution to the medical arts.